crossing96/oncoscreening huggingface dataset:
Risk factors for development of primary bladder squamous cell carcinoma.	INTRODUCTION The aim of this study was to investigate the prevalence of risk factors for primary squamous cell carcinoma (SCC) of the bladder. MATERIALS A total of 90 cases of primary SCC of the bladder were identified through multicentre analysis. Patient demographics, stage and grade of cancer at presentation, management and outcomes were recorded. The presence of known risk factors (catheter use, neuropathic bladder, smoking history, recurrent urinary tract infection and bladder stones) was also documented. RESULTS Over half of the patients had at least one identifiable risk factor for the development of primary bladder SCC: 13.9% of patients had a history of catheter use (clean intermittent self-catheterisation [CISC] in 11.1%), 10.0% of patients had a neuropathic bladder, 27.8% were smokers or ex-smokers and 20.0% had a documented history of recurrent urinary tract infection. Statistical analysis of the results showed no association between risk factors and grade of tumour at presentation. CONCLUSIONS These data further support the association between primary bladder SCC and several of the well documented risk factors for its development. Chronic use of CISC may confer a greater risk for development of SCC than thought previously. Further evidence of the role of CISC in primary SCC is required to justify routine screening and to determine exactly when surveillance of the bladder should begin for this group of patients.	bladder
This Month in AJP.	The following highlights summarize research articles that are published in the current issue of The American Journal of Pathology.	bladder
A microRNA biomarker panel for the non-invasive detection of bladder cancer.	The development of accurate, non-invasive urinary assays for bladder cancer would greatly facilitate the detection and management of a disease that has a high rate of recurrence and progression. In this study, we employed a discovery and validation strategy to identify microRNA signatures that can perform as a non-invasive bladder cancer diagnostic assay. Expression profiling of 754 human microRNAs (TaqMan low density arrays) was performed on naturally voided urine samples from a cohort of 85 subjects of known bladder disease status (27 with active BCa). A panel of 46 microRNAs significantly associated with bladder cancer were subsequently monitored in an independent cohort of 121 subjects (61 with active BCa) using quantitative real-time PCR (RT-PCR). Multivariable modeling identified a 25-target diagnostic signature that predicted the presence of BCa with an estimated sensitivity of 87% at a specificity of 100% (AUC 0.982). With additional validation, the monitoring of a urinary microRNA biomarker panel could facilitate the non-invasive evaluation of patients under investigation for BCa.	bladder
Heterogeneous nuclear ribonucleoprotein K is associated with poor prognosis and regulates proliferation and apoptosis in bladder cancer.	Heterogeneous nuclear ribonucleoprotein K (hnRNPK) is an essential RNA- and DNA-binding protein that regulates diverse biological events, especially DNA transcription. hnRNPK overexpression is related to tumorigenesis in several cancers. However, both the expression patterns and biological mechanisms of hnRNPK in bladder cancer are unclear. We investigated hnRNPK expression by immunohistochemistry in 188 patients with bladder cancer, and found that hnRNPK expression levels were significantly increased in bladder cancer tissues and that high-hnRNPK expression was closely correlated with poor prognosis. Loss- and gain-of-function assays demonstrated that hnRNPK promoted proliferation, anti-apoptosis, and chemoresistance in bladder cancer cells in vitro, and hnRNPK knockdown suppressed tumorigenicity in vivo. Mechanistically, hnRNPK regulated various functions in bladder cancer by directly mediating cyclin D1, G0/G1 switch 2 (G0S2), XIAP-associated factor 1, and ERCC excision repair 4, endonuclease catalytic subunit (ERCC4) transcription. In conclusion, we discovered that hnRNPK plays an important role in bladder cancer, suggesting that it is a potential prognostic marker and a promising target for treating bladder cancer.	bladder
Evaluation of double immunocytochemical staining for CK20 and P53 as a potential adjunct to cytology for urothelial cancer diagnosis.	OBJECTIVE: To evaluate double immunocytochemical staining with p53 and CK20, as a tool for improving the accuracy of urinary cytology. The aim of the present study was to clarify the diagnostic significance of the expression of these markers and to investigate the possibility of using this information for better monitoring of bladder cancer patients during follow-up. MATERIAL AND METHODS: One hundred and twenty-five urine cytology cases were retrieved with corresponding histology from our files. One ThinPrep® smear was available for each of them and dual immunocytological staining for p53 and CK20 was performed. Eleven cases were excluded from the study because of hypocellularity. The material comprised 58 malignant, 36 atypical and 20 negative for malignancy cases. Immunocytochemistry was evaluated by two cytopathologists, blinded to the histological diagnosis or follow-up data. A cut-off threshold of five stained atypical cells, according to the literature, was used for evaluation. RESULTS: Fifty-two out of 58 malignant cases were positive for at least one of the markers (89.6%). In the atypical and negative groups, 18 (50%) and 5 (25%) cases were positive, respectively. Accuracy parameters evaluation for cytology versus the combination of cytology with immunocytological staining were: sensitivity 73.4% versus 91.1%, specificity 100% versus 74.3%, positive predictive value (PPV) 100% versus 88.9% and negative predictive value (NPV) 62.5% versus 78.8%. CONCLUSIONS: Double immunocytochemical staining for p53 and CK20 is easy to perform and evaluate and can improve cytology sensitivity. It is helpful in establishing a diagnosis of malignancy and may be used as a triage tool to select patients that require cystoscopy during clinical follow-up.	bladder
Downregulated KLK13 expression in bladder cancer highlights tumor aggressiveness and unfavorable patients' prognosis.	PURPOSE: Despite recent research advantages on the molecular and subcellular background, bladder cancer (BlCa) remains a clinically neglected malignancy. This is strongly reflected by the generic approach of disease diagnosis and management. Additionally, patients' prognosis became a rather demanding task due to the great disease heterogeneity. Here, we aimed to evaluate, for the first time, the clinical value of KLK13 in BlCa. METHODS: A total of 279 bladder specimens (137 tumors, 107 adjacent normal tissues and 35 healthy samples) were included. Total RNA was extracted, reverse transcribed, and KLK13 expression was assessed by quantitative real-time PCR. RESULTS: KLK13 expression is significantly increased in bladder tumors compared to normal adjacent epithelium. However, reduced KLK13 expression is correlated with disease aggressiveness, including higher tumor stage and grade, and high-risk TaT1 tumors according to the EORTC stratification. Moreover, Kaplan-Meier and Cox regression analysis highlighted the prognostic value of the reduced KLK13 expression for the prediction of TaT1 patients' recurrence and shorter disease-free survival following TURBT. Finally, the combination of KLK13 expression with EORTC-risk stratification results to an improved prediction of TaT1 patients' outcome. CONCLUSION: This first clinical study of KLK13 in BlCa reveals its deregulated expression in bladder tumors and highlights KLK13 as a promising marker for improving TaT1 patients' prognosis following treatment.	bladder
[Expression of PAK1 in bladder cancer and its influence on invasion of bladder cancer cells].	Objective: To investigate the expression of p21-activated kinase 1 (PAK1) in bladder cancer and its biological influence on invasion ability of bladder cancer cells. Methods: A total of 54 paraffin-embedded bladder cancer tissue samples and 12 normal bladder tissue specimens were retrieved in Jinshan Hospital Affiliated to Fudan University between January 2009 and December 2012. The expression of PAK1 in these tissues was detected by immunohistochemical staining. The PAK1 mRNA and protein levels were measured in bladder cancer cell lines and human normal bladder epithelial cell line using real-time, fluorescence-based quantitative polymerase chain reaction (RT-PCR) and Western blot, respectively. A stable PAK1 gene silencing bladder cancer cell strain 5637 were successfully constructed. After treatment with PAK1 RNA interference(RNAi), the ability of migration and invasion of the 5637 cell was evaluated using a Transwell system. Results: The expression of PAK1 proteins was significantly higher in bladder cancer tissues than in normal bladder tissues (28/54 vs 1/12, P<0.05). The overexpression of PAK1 was positively correlated with high histological grade, lymph node metastasis, and tumor size (all P<0.05). The mRNA level and protein level of PAK1 was much higher in bladder cancer cell lines T24, 5637 than human normal urothelial cell line SV-HUC-1.PCR and Western blot showed satisfactory inhibitory effect of PAK1 short hairpin RNA (shRNA) on PAK1 expression in 5637 bladder cancer cells. The number of PAK1 RNAi-treated 5637 cells traversed the membrane was decreased compared with the control group in migration and invasion assays. Conclusions: Overexpression of PAK1 in bladder cancer tissues may be an important feature of bladder cancer and related with the metastasis and invasion of bladder cancer. The molecular mechanisms involved in regulation of PAK1 expression needs further research.	bladder
Specific micro-RNA expression patterns distinguish the basal and luminal subtypes of muscle-invasive bladder cancer.	"The roles of non-coding RNAs in controlling clinical and biological heterogeneity in bladder cancer remain unclear. We used TCGA's published dataset (n = 405 tumors) as a discovery cohort and created a new validation cohort to define the miRNA expression patterns in the basal and luminal molecular subtypes of muscle-invasive bladder cancer (MIBC). We identified 63 miRNAs by PAM, which optimally identified basal and luminal tumors. The targets of the top luminal miRNAs were activators of EMT (ZEB1, ZEB2) and basal subtype transcription (IL-6, EGFR, STAT3), whereas the targets of the top basal miRNAs were involved in adipogenesis pathways and luminal breast cancer (ERBB2, ERBB3). We also identified a 15-miRNA signature that identified stromally infiltrated basal and luminal MIBCs corresponding to the ""cluster IV/immune undifferentiated/claudin-low"" and ""cluster II/luminal immune"" subtypes identified previously, which likely contain samples with higher infiltration rates. Using the 63-miRNA signature, we accurately assigned MIBCs to the basal and luminal subtypes and confirmed that patients with basal tumors had shorter overall survival. The results strongly suggest that miRNAs contribute to the control of the gene expression patterns observed in basal and luminal MIBCs and that they can be used as biomarkers and candidate therapeutic targets."	bladder
Emerging role of immunotherapy in urothelial carcinoma-Immunobiology/biomarkers.	Urothelial bladder cancer is one of the first cancers recognized to be immunogenic since 40 years ago when the use of bacillus Calmette-Guerin was shown to prevent recurrence. Since that time, our knowledge of immune biology of cancer has expanded tremendously, and patients with bladder cancer finally have new active immunotherapeutic drugs on the horizon. Anti-programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) therapy has shown impressively durable responses in urothelial bladder cancer (UBC), but the reported response rates warrant improvement. To outline potential strategies to overcome tumor immune resistance, herein, we summarize current models of tumor immunology with a specific focus on bladder cancer. Recognition of tumor-specific antigens through cross-presentation, T-cell priming and activation, and trafficking of immune cells to the tumor microenvironment are some of the critical steps we now understand to be necessary for an effective antitumor immune response. Many of the involved steps are important targets for therapeutic interventions. As new immunotherapies are developed, predictive biomarkers would also be important to select patients most likely to respond and to better understand tumor biology. Several potential biomarkers are reviewed including PD-L1 expression, identification of T-cell-inflamed/non-T-cell-inflamed tumors based on immune gene expression, intrinsic molecular subtyping based on luminal/basal or the cancer genome atlas (TCGA) groups, T-cell receptor sequencing, and somatic mutational density. Even within the past few years, our current knowledge of immune biology has exploded, and we are highly optimistic about the future of UBC therapy that will be available to patients.	bladder
Dysregulated expression of homebox gene HOXA13 is correlated with the poor prognosis in bladder cancer.	BACKGROUND: The homeobox (HOX) genes have been implicated playing important roles in many human cancers. HOXA13 is a member of HOX genes that encode transcription factors regulating embryonic development and cell fate. In the present study, we aimed to investigate the expression and prognostic significance of HOXA13 in bladder cancer. METHODS: Immunohistochemical staining was initially performed to screen the differentially expressed HOXA13 between bladder cancer tissues and paired adjacent non-cancerous tissues. Subsequent Western blotting analysis validation was conducted using tissue samples from patients with bladder cancer. RESULTS: The expression level of HOXA13 was significantly higher in bladder cancer tissues compared to that in adjacent non-cancerous tissues (P < 0.001). The χ(2)-test showed that expression of HOXA13 was positively correlated with lymphatic metastasis (P = 0.013), bladder tumor TNM stage (P = 0.002) and pathological grade (P < 0.001). Kaplan-Meier survival analysis revealed that patients with bladder cancer with high expression of HOXA13 had shorter overall survival time (P = 0.001) and disease-free survival time (P = 0.001) compared to patients with low expression of HOXA13. Multivariate analysis indicated that HOXA13 was an independent prognostic factor for overall survival for bladder cancer patients. CONCLUSIONS: The results of our study show that high expression of HOXA13 is associated with the progression of bladder cancer and that HOXA13 might serve as a biomarker for prognosis of bladder cancer.	bladder
Elevated preoperative plasma fibrinogen level is an independent predictor of malignancy and advanced stage disease in patients with bladder urothelial tumors.	PURPOSE: To investigate the association between preoperative plasma fibrinogen levels and clinicopathological features in patients with bladder urothelial tumors. METHODS: In this retrospective single-center study, we evaluated preoperative plasma fibrinogen levels in 503 patients newly diagnosed with bladder urothelial tumors between January 2009 and October 2014. All patients received surgical intervention as the primary treatment method. Associations between preoperative plasma fibrinogen levels and clinicopathological parameters were analyzed. Univariate and multivariate logistic regression analyses were performed to identify independent associations. RESULTS: The mean preoperative fibrinogen level in patients with bladder urothelial carcinoma (BUC) was significantly higher than that in patients with papilloma or papillary urothelial neoplasm of low malignant potential (PUNLMP) (P = 0.004). Additionally, patients with BUC with advanced-stage disease showed elevated plasma fibrinogen levels compared to patients with early-stage disease (high-grade BUC vs. low-grade BUC: P = 0.002; muscle-invasive BUC vs. non-muscle-invasive BUC: P = 0.010). In a multivariate regression model, a plasma fibrinogen level >3.04 g/L was identified to be independently associated with the presence of BUC (hazard ratio [HR] = 1.653, P = 0.047), high-grade BUC (HR = 1.869, P = 0.004), and muscle-invasive BUC (HR = 1.870, P = 0.044). CONCLUSIONS: Elevated preoperative plasma fibrinogen level is an independent predictor of malignancy as well as advanced-stage carcinoma in patients with bladder urothelial tumors, suggesting that plasma fibrinogen may be a promising diagnostic and prognostic biomarker for bladder tumors.	bladder
Agricultural exposure and risk of bladder cancer in the AGRIculture and CANcer cohort.	PURPOSE: Literature on agricultural activities and bladder cancer risk is scarce. However, farmers can be subjected to carcinogenic exposure (e.g. arsenic, previously used as a pesticide in France). This study aimed at assessing the role of a large range of agricultural activities and tasks on bladder cancer risk. METHODS: The study population was the AGRIculture and CANcer cohort, a large prospective cohort of individuals affiliated to the agricultural health insurance scheme (MSA) in France. Incident bladder cancers were identified by cancer registries from enrolment (2005-2007) to 2009. Data on agricultural exposure during professional lifetime (5 animals, 13 crops, specific tasks) were obtained from the enrolment questionnaire. Associations between bladder cancer and agricultural exposure were analysed using a Cox model, adjusted for gender and smoking history. RESULTS: Among the 148,051 farm owners and workers included in this analysis, 179 incident bladder cancers were identified. We observed an elevated risk among field-grown vegetable workers [HR 1.89, 95% CI (1.20-2.99)], with an exposure-response relationship with duration of work [≥30 years: HR 2.54, 95% CI (1.11-5.83), p-trend = 0.02], and higher risk among women [HR 3.82, 95% CI (1.58-9.25), p-interaction = 0.05]. Non-significantly increased risks were also observed in greenhouse farmers (HR = 1.95), pea sowing (HR = 1.84), rape sowing (HR = 1.64); several tasks involving pesticide use, especially seed treatment (HR = 1.24); and in activities and tasks potentially exposing to arsenic compounds via pesticide use (HR = 1.49) or re-entry tasks (HR = 1.63). CONCLUSIONS: Our analyses raise the question of a possible link between agricultural activity, especially field-grown vegetables, and greenhouse cultivation and bladder cancer.	bladder
mTORC2 activation is regulated by the urokinase receptor (uPAR) in bladder cancer.	Mammalian target of rapamycin complex 2 (mTORC2) has been identified as a major regulator of bladder cancer cell migration and invasion. Upstream pathways that mediate mTORC2 activation remain poorly defined. Urokinase-type plasminogen activator receptor (uPAR) is a GPI-anchored membrane protein and known activator of cell-signaling. We identified increased uPAR expression in 94% of invasive human bladder cancers and in 54-71% of non-invasive bladder cancers, depending on grade. Normal urothelium was uPAR-immunonegative. Analysis of publicly available datasets identified uPAR gene amplification or mRNA upregulation in a subset of bladder cancer patients with reduced overall survival. Using biochemical approaches, we showed that uPAR activates mTORC2 in bladder cancer cells. Highly invasive bladder cancer cell lines, including T24, J82 and UM-UC-3 cells, showed increased uPAR mRNA expression and protein levels compared with the less aggressive cell lines, UROtsa and RT4. uPAR gene-silencing significantly reduced phosphorylation of Serine-473 in Akt, an mTORC2 target. uPAR gene-silencing also reduced bladder cancer cell migration and Matrigel invasion. S473 phosphorylation was observed by immunohistochemistry in human bladder cancers only when the tumors expressed high levels of uPAR. S473 phosphorylation was not controlled by uPAR in bladder cancer cell lines that are PTEN-negative; however, this result probably did not reflect altered mTORC2 regulation. Instead, PTEN deficiency de-repressed alternative kinases that phosphorylate S473. Our results suggest that uPAR and mTORC2 are components of a single cell-signaling pathway. Targeting uPAR or mTORC2 may be beneficial in patients with bladder cancer.	bladder
Diagnostic Ureteroscopy for Upper Tract Urothelial Carcinoma is Independently Associated with Intravesical Recurrence after Radical Nephroureterectomy.	PURPOSE: To determine the effect of diagnostic ureteroscopy on intravesical recurrence in patients with upper tract urothelial carcinoma (UTUC) after radical nephroureterec¬tomy (RNU). MATERIALS AND METHODS: We conducted a retrospective analysis of 664 patients who were treated with RNU for UTUC from June 2000 to December 2011, excluding those who had concomitant/prior bladder tumors. Of the 664 patients, 81 underwent di¬agnostic ureteroscopy (URS). We analyzed the impact of diagnostic ureteroscopy on intravesical recurrence (IVR) using the Kaplan-Meier method. Univariate and multi¬variate analyses were used to determine the independent risk factors. RESULTS: The median follow-up time was 48 months (interquartile range (IQR): 31- 77 months). Patients who underwent ureteroscopy were more likely to have a small (p<0.01), early-staged (p=0.019), multifocality (p=0.035) and ureteral tumor (p<0.001). IVR occurred in 223 patients during follow-up within a median of 17 months (IQR: 7-33). Patients without preoperative ureteroscopy have a statistically significant better 2-year (79.3%±0.02 versus 71.4%±0.02, p<0.001) and 5-year intravesical recurrence-free survival rates (64.9%±0.05 versus 44.3%±0.06, p<0.001) than patients who un¬derwent ureteroscopy. In multivariate analysis, the diagnostic ureteroscopy (p=0.006), multiple tumors (p=0.001), tumor size <3cm (p=0.008), low-grade (p=0.022) and pN0 stage tumor (p=0.045) were independent predictors of IVR. CONCLUSIONS: Diagnostic ureteroscopy is independently associated with intravesical re¬currence after radical nephroureterectomy.	bladder
Network-Based Biomedical Data Analysis.	Complex diseases are caused by disorders of both internal and external factors, and they account for a large proportion of human diseases. They are multigenetic and rarely a consequence of the dysfunction of single molecules. Systems biology views the living organism as an organic network. Compared with reductionism-based viewpoints, systems biology pays more attention to the interactions among molecules located at different omics levels. Based on this theory, the concepts of network biomarkers and network medicine have been proposed sequentially, which integrate clinical data with knowledge of network sciences, thereby promoting the investigation of disease pathogenesis in the era of biomedical informatics. The former aims to identify precise signals for disease diagnosis and prognosis, whereas the latter focuses on developing effective therapeutic strategies for specific patient cohorts. In this chapter, the basic concepts of systems biology and network theory are presented, and clinical applications of biomolecular networks, network biomarkers, and network medicine are then discussed.	bladder